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Event: 1985

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increased Kisspeptin levels in anteroventral periventricular nucleus (AVPV)

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

Increased Kisspeptin levels in AVPV

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Biological Context

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Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Cell term
neuron

Organ term

Organ term
hypothalamus

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
neurotransmitter secretion	Metastin	increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
ERα Agonism leads to Impaired Reproduction	KeyEvent	John Hoang (send email)	Under development: Not open for comment. Do not cite
Activation, ERα leads to persistent vaginal cornification via increased kisspeptin	KeyEvent	John Frisch (send email)	Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Term	Scientific Term	Evidence	Link
mammals	mammals	Moderate	NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
Adult, reproductively mature	Moderate
Juvenile	Moderate

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Unspecific	High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

This Key Event represents increased kisspeptin levels measured in the anteroventral periventricular nucleus. Kisspeptin (also known as metastin) is a key signalling neuropeptide hormone in mammals and some other vertebrates. The kisspeptin gene (KISS1) encodes a 145 amino acid prepolypeptide that is converted to 4 active peptides with names based on the number of amino acids (kisspeptin-54, 14, 13, 10); each active peptide is able to activate kisspeptin receptor (GPR54, KISS1R) because of a conserved c-terminal region Arg-Phe-NH2 group (Hu et al. 2018). Positive feedback for kisspeptin hormone production is due to increased levels of estrogen binding to Estrogen Receptor Alpha (ERa) receptors in neurons from the anteroventral periventricular nucleus (AVPV) region of the hypothalamus (Uenoyama et al. 2021).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Kisspeptin can be measured via immunoassay or Western blotting in vivo (studies that utilized this approach include Adachi et al. 2007; Clarkson et al. 2008; Wang et al. 2014), and include commercially available ELISA kits (e.g. Abcam ab288589 (human); Assay Genie HUDL01615 (human); LS Bio LS-F8897 (mouse)). Mention of trade names or commercial products does not constitute endorsement or recommendation for use.

Real time PCR can be used to measure kisspeptin transcript abundance, which is an indirect – and only semi-quantitative indicator of kisspeptin hormone levels (studies that utilized this approach include Adachi et al. 2007; Tomikawa et al. 2012; Wang et al. 2014).

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Life Stage: Adult, reproductively mature, juveniles.

Sex: Applies to both males and females as both sexes require kisspeptin signalling for regulation of various hormone pathways.

Taxonomic: Primarily studied in laboratory rodents and humans. Plausible for most mammals due to conserved hormone pathways regulating hypothalamus-pituitary-gonadal axis processes. For vertebrates, kisspeptins and kisspeptin receptors are absent from bird species; present in mammals and fish (Sivalingam et al. 2022).

References

List of the literature that was cited for this KE description. More help

Adachi S, Yamada S, Takatsu Y, Matsui H, Kinoshita M, Takase K, Sugiura H, Ohtaki T, Matsumoto H, Uenoyama Y, Tsukamura H, Inoue K, Maeda K. 2007. Involvement of anteroventral periventricular metastin/kisspeptin neurons in estrogen positive feedback action on luteinizing hormone release in female rats. Journal of Reproduction and Development 53(2): 367-378.

Clarkson J, d’Anglemont de Tassigny X, Moreno AS, Colledge WH, Herbison AE. 2008. Kisspeptin–GPR54 signaling is essential for preovulatory gonadotropin-releasing hormone neuron activation and the luteinizing hormone surge. Journal of Neuroscience 28(35): 8691–8697.

Hu KL, Zhao H, Chang HM, Yu Y, Qiao J. 2018. Kisspeptin/Kisspeptin Receptor System in the Ovary. Frontiers in Endocrinology 8: 365.

Sivalingam M, Ogawa S, Trudeau VL, Parhar IS. 2022. Conserved functions of hypothalamic kisspeptin in vertebrates. General and Comparative Endocrinology 317: 113973.

Tomikawa J, Uenoyama Y, Ozawa M, Fukanuma T, Takase K, Goto T, Abe H, Ieda N, Minabe S, Deura C, Inoue N, Sanbo M, Tomita K, Hirabayashi M, Tanaka S, Imamura T, Okamura H, Maeda K, Tsukamura H. 2012. Epigenetic regulation of Kiss1 gene expression mediating estrogen-positive feedback action in the mouse brain. Proceedings of the National Academy of Science 109(20): E1294-E1301.

Uenoyama, Y., Inoue, N., Nakamura, S., and Tsukamura, H. Kisspeptin Neurons and Estrogen–Estrogen Receptor α Signaling: Unraveling the Mystery of Steroid Feedback System Regulating Mammalian Reproduction. 2021. International Journal of Molecular Sciences 22(17): 9229.

Wang X, Chang F, Bai Y, Chen F, Zhang J, Chen L. 2014. Bisphenol A enhances kisspeptin neurons in anteroventral periventricular nucleus of female mice. Journal of Endocrinology 28(35): 201-213.

NOTE: Italics indicate edits from John Frisch January 2026. A full list of updates can be found in the Change Log on the View History page.